Extracellular Matrix: Basement Membranes

Basement membranes (BMs) are thin sheets of specialized extracellular matrix that underlie endothelial and epithelial cells and surround all muscle cells, fat cells, and peripheral nerves. They play important roles in filtration, compartmentalization within tissues, maintenance of epithelial integrity, and they influence cell proliferation, differentiation, migration, and survival. In the lung, BMs are associated with bronchial and vascular smooth muscle cells, bronchial epithelium, nerve, pleura, and they are part of the air-blood barrier between microvascular endothelial cells and alveolar epithelial cells. Collagen IV and laminin are the major components of all basement membranes, which also contain entactin/nidogen and various heparan sulfate proteoglycans, including perlecan. Two collagen IV heterotrimeric protomers, (α1)2α2 and α3α4α5, are found in basement membranes, the former in all lung BMs, the latter only in alveolar BMs. Laminin chains exhibit temporal and spatial specificity in different lung BMs. Knockout and mutant mouse models reveal important roles for collagen IV and laminins in lung development with those surviving to birth exhibiting defects in sacculation, septation, and epithelial cell differentiation. In human lung disease, the α3 chain of collagen IV contains the epitope that is attacked in Goodpasture’s syndrome, an autoimmune disease characterized by pulmonary hemorrhage and glomerulonephritis. While no laminin chain has been directly implicated in human lung disease, recent studies suggest potential roles in mechanical injury, asthma, and lung cancer mortality.